Two breakthroughs in stem cell research

Two important breakthroughs in stem cell biology were reported recently. First, some background. There are two kinds of stem cells (SC): adult (somatic) and embryonic. Adult SC come from adult tissue. Embryonic SC are obtained from the inner cells of a blastocyst, a ball of cells formed 5 to 7 days after fertilization of an egg. As opposed to adult stem cells, embryonic SC are pluripotent, i.e. they can differentiate into any cells in our body and cultured in a lab dish to produce millions of specialized cells which have potential to replace damaged or diseased tissues.

With the Bush administration’s ban on federal funding for research with new human embryonic SC lines, most experiments have been done with embryonic SC from other mammals with preliminary but promising results. For example, neurons from mouse embryonic SC have been used to treat Parkinson’s disease and spinal cord injuries, pancreatic beta cells to treat diabetes, and cardiomyocytes to repair heart muscle, all in mice.

However, differentiated cells from the SC of one individual, used to treat a different individual, can be rejected by the recipient’s immune system. This problem can be overcome by “somatic cell nuclear transfer” (SCNT) whereby the nucleus from a normal (patient’s) cell, e.g. skin cell, is transferred to an enucleated egg cell and then stimulated to generate embryonic SCs with a genetic match of the patient.

SCNT had been successful with mouse cells, but until recently not with primate cells. In November researchers from Oregon reported successful SCNT with monkey cells making it likely that SCNT can be successful in human cells. However, they used 304 eggs from 14 rhesus monkeys to generate just two embryonic SC lines. Human therapies will require far fewer eggs.

A second major breakthrough was announced one week later. Investigators in Japan and, independently, in Wisconsin, reported that adult human cells, e.g. skin cells, could be reprogrammed to generate pluripotent stem cells. The Japanese had shown earlier that mouse somatic cells could be so programmed by introduction of four specific genes. Their recent paper showed that the same four worked with human somatic cells. An adult differentiated cell from an individual has his/her genomic DNA in the generated stem cell, eliminating need for SCNT.

However, in this procedure also, problems need solving before used in therapies. Introduction of the four genes into the somatic cell was mediated by retroviral transduction, i.e. the viral genome with the inserted gene acted as a “vector” to enter the cell. Three to six such insertions of each gene were to random sites in the cell’s genome which increased the risk of tumorigenesis. In the mouse experiments about 20 percent of the recipient mice developed tumors. The vector cannot pose a risk of tumor development.

Although not discussed, insertion of these genes at random sites also poses the possibility of disrupting normal gene expression. Random insertion of genes in genetically engineered plant crops has been a concern for many years, since other inheritable traits could be affected. The authors note that it might be possible to induce the four genes in the cell’s genome with small molecules that can enter the cells, so the genes would not have to be transferred into the cell. That would be much safer.

It is ironic that opponents of embryonic SC research, including President Bush, have hailed the latter breakthrough as proof that science has shown that pluripotent stem cells can be derived without destroying humans, i.e. destroying the tiny blastocyst about the size of this period.

First, without the research with embryonic SC, there wouldn’t have been these studies on somatic cells. In fact, Dr. James Thomson, who first identified embryonic SC in 1998, was senior author in the Wisconsin group that reprogrammed somatic cells. He felt the political controversy set the field back four or five years. Second, proponents of embryonic SC research have supported research in all areas of stem cell biology and welcome these findings.

Regardless of which procedure will ultimately be the most effective for therapies, the various lines of study will continue to complement each other and hasten progress.

Most important, science should not be restricted by religious dogma. Many religions and religious leaders (including some catholic theologians) do not agree that humans have a “soul” upon fertilization of the human egg. Even if all did, religious dogma should not be a weapon to stifle scientific research, in this case research that holds promise to alleviate many dread diseases and prolong human life.

David Kennell (kennell @borcim.wustl.edu) is professor emeritus of molecular microbiology at Washington University School of Medicine in St. Louis.